Structural characterization of antibiotic self-immunity tRNA synthetase in plant tumour biocontrol agent
| Autor: | John S. Reader, Cornelia Virus, Sarah Schulwitz, Shaileja Chopra, Brenda Temple, Andrés Palencia, Stephen Cusack |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.drug_class Science Mutant Antibiotics General Physics and Astronomy Mutagenesis (molecular biology technique) medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology Microbiology Evolution Molecular 03 medical and health sciences RNA Transfer Plant Tumors Drug Resistance Bacterial medicine Pest Control Biological Pathogen Gene Multidisciplinary biology Toxin fungi General Chemistry biology.organism_classification Kinetics 030104 developmental biology Agrobacterium tumefaciens Genes Bacterial Leucine-tRNA Ligase Bacteria Agrobacterium radiobacter |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-13 (2016) 'Nature Communications ', vol: 7, pages: 12928-1-12928-13 (2016) |
| ISSN: | 2041-1723 |
| DOI: | 10.17615/v7ap-3w36 |
| Popis: | Antibiotic-producing microbes evolved self-resistance mechanisms to avoid suicide. The biocontrol Agrobacterium radiobacter K84 secretes the Trojan Horse antibiotic agrocin 84 that is selectively transported into the plant pathogen A. tumefaciens and processed into the toxin TM84. We previously showed that TM84 employs a unique tRNA-dependent mechanism to inhibit leucyl-tRNA synthetase (LeuRS), while the TM84-producer prevents self-poisoning by expressing a resistant LeuRS AgnB2. We now identify a mechanism by which the antibiotic-producing microbe resists its own toxin. Using a combination of structural, biochemical and biophysical approaches, we show that AgnB2 evolved structural changes so as to resist the antibiotic by eliminating the tRNA-dependence of TM84 binding. Mutagenesis of key resistance determinants results in mutants adopting an antibiotic-sensitive phenotype. This study illuminates the evolution of resistance in self-immunity genes and provides mechanistic insights into a fascinating tRNA-dependent antibiotic with applications for the development of anti-infectives and the prevention of biocontrol emasculation. The bacterium Agrobacterium radiobacter K84 secretes an antibiotic that is transported into the plant pathogen A. tumefaciens and processed into the toxin TM84. Here, the authors identify a mechanism whereby the antibiotic-producing microbe resists its own toxin. |
| Databáze: | OpenAIRE |
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